A new in vivo electrochemical technique for monitoring CNS catecholamines will be investigated and improved. This technique makes possible in freely moving animals the selective anatomical monitoring of neurotransmitters implicated in human psychological disorders such as schizophrenia. The specific aims of the proposed research are: 1) to improve the existing microelectrode used to measure neurotransmitters, 2) to assess the validity of recording from these electrodes for a number of days by using amphetamine-stimulated dopamine release, 3) to evaluate the effect of different current-time sampling procedures on baseline levels of neurotransmitters, and 4) to demonstrate a neuroanatomically localized, quantitative dose-response curve of neurotransmitter release caused by administration of methylphenidate. A computerized system will be used for the control and monitoring of the in vivo electrochemistry. Information derived from the objectives outlined above is essential to future work in which in vivo monitoring of neurotransmitters is used for assessment of drug-brain mechanisms, synergistic effects of drugs and alcohol as well as other toxic substances, and for screening of new neuroleptic drugs.